What is the management of Glioblastoma Multiforme (GBM)?

From the Guidelines

The management of glioblastoma multiforme (GBM) should involve a multimodal approach, including maximal safe surgical resection, followed by concurrent chemoradiation therapy with temozolomide, as this approach has been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with newly diagnosed GBM, particularly those with MGMT promoter-methylated tumors 1. The standard treatment regimen includes radiotherapy (60 Gy in 30 fractions over 6 weeks) with concurrent temozolomide (75 mg/m² daily during radiation), followed by adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days for 6-12 cycles). For elderly patients or those with poor performance status, hypofractionated radiotherapy may be used, with the addition of temozolomide also shown to improve OS in patients aged ≥60 years 1. Some key points to consider in the management of GBM include:

• The use of tumor treating fields (TTFields) therapy, delivered by the Optune device, which can be added after chemoradiation to improve survival
• The management of cerebral edema with corticosteroids, such as dexamethasone, which should be tapered to the lowest effective dose
• The use of antiseizure medications, such as levetiracetam, in patients who have experienced seizures
• Regular MRI monitoring every 2-3 months to assess treatment response Despite optimal therapy, GBM has a high recurrence rate, with options for recurrent disease including re-resection, re-irradiation, bevacizumab, or enrollment in clinical trials 1. The choice of treatment should be individualized based on patient factors, such as age, performance status, and MGMT promoter methylation status, as well as tumor characteristics, such as size and location. Overall, the goal of treatment is to improve OS and quality of life, while minimizing toxicity and preserving neurological function.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Newly Diagnosed Glioblastoma Multiforme

Five hundred and seventy-three patients were randomized to receive either temozolomide (TMZ)+Radiotherapy (RT) (n=287) or RT alone (n=286). Patients in the temozolomide+RT arm received concomitant temozolomide (75 mg/m 2) once daily, starting the first day of RT until the last day of RT, for 42 days (with a maximum of 49 days) This was followed by 6 cycles of temozolomide alone (150 or 200 mg/m 2) on Days 1 to 5 of every 28-day cycle, starting 4 weeks after the end of RT. The addition of concomitant and maintenance temozolomide to radiotherapy in the treatment of patients with newly diagnosed GBM showed a statistically significant improvement in overall survival compared to radiotherapy alone ( Figure 1).

The management of Glioblastoma Multiforme (GBM) involves the use of temozolomide in combination with radiotherapy (RT). The recommended dosing is 75 mg/m² once daily during RT, followed by 6 cycles of temozolomide alone (150 or 200 mg/m²) on Days 1 to 5 of every 28-day cycle. This treatment regimen has shown a statistically significant improvement in overall survival compared to RT alone 2. Key components of the treatment include:

• Concomitant temozolomide and RT
• Maintenance temozolomide after RT
• Dosing of 75 mg/m² during RT and 150 or 200 mg/m² during maintenance cycles.

From the Research

Management of Glioblastoma Multiforme (GBM)

The management of GBM is a complex process that requires a multidisciplinary approach, involving neuro-oncology, neurosurgery, radiation oncology, and pathology 3. The following are some key aspects of GBM management:

• Surgical resection is an integral part of the treatment plan, aiming to establish a histopathologic diagnosis and achieve safe, maximal, and feasible tumor resection 3
• Postoperative external-beam radiotherapy is recommended as standard therapy for patients with GBM, with a recommended dose of 60 Gy in 2-Gy fractions 3
• Concurrent chemoradiation with temozolomide is a standard treatment approach, followed by adjuvant temozolomide 3, 4
• The management of GBM should be highly individualized, taking into account the patient's medical history, functional status, and tumor location 3

Treatment Options

Various treatment options are available for GBM, including:

• Surgery: maximal safe surgical resection is the primary treatment approach 3, 5, 6
• Radiotherapy: external-beam radiotherapy is a standard treatment approach, with a recommended dose of 60 Gy in 2-Gy fractions 3
• Chemotherapy: temozolomide is a commonly used chemotherapeutic agent, administered concurrently with radiotherapy and as adjuvant therapy 3, 4
• Targeted therapy: various targeted therapies are being investigated, including anti-angiogenic therapy and immunotherapy 5, 6
• Immunotherapy: immunotherapeutic approaches are being explored, but have yet to show a significant survival advantage 6

Challenges and Future Directions

The management of GBM is challenging due to the tumor's complexity, genetic heterogeneity, and protection by the blood-brain barrier 5, 7. Future directions for GBM management include:

• Improving existing treatment approaches, such as surgical techniques and chemoradiation regimens 3, 6
• Investigating new treatment alternatives, including targeted therapy, immunotherapy, and nanotherapy 5, 6
• Developing innovative treatment strategies to overcome resistance mechanisms and improve patient outcomes 7